Substituted dihydropyrimidinone compounds has excellent activity against the viruses of the trachoma group. Some of the analogs of Dihydropyrimidine compounds are antitumour agents and formed to be active against Walker carcinosarcoma in rats and mice. The cardiovascular activity of Biginelli compounds, namely of β-amino ethyl ester was first discovered by Khanina and co-workers in 1978. Since 1986 the number of publications and patents dealing with the cardiovascular activity of dihydropyrimidine has grown rapidly.
Dihydropyrimidinones have emerged as the integral back-bones of calcium channel blockers (a. Rovnyak, G. C et al, J. Med. Chem., 1995, vol 38, p-119–129; b. Atwal, K. S et al J. Med. Chem., 1990, vol 33, p-2629–2635), antihypertensive agents (Atwal, K. S et al, J. Med. Chem., 1991, vol 34, p-806–811), α-adrenergic and neuropeptide Y (NPY) antagonists.
Several marine alkaloids containing the dihydropyrimidine core unit have shown interesting biological properties (a. Overman L. E et al J. Am. Chem. Soc., 1995, vol 117, p-2657–2658; b. Snider, B. B et al J. Org. Chem., 1993, vol 58, p-3828–3839). Batzelladine alkaloids have been found to be potent HIV gp-120-CD4 inhibitors (a. Snider, B. B et al Tetrahedron Lett., 1996, vol 37, p-6977–6980; b. Patil, A. D et al J. Org. Chem., 1995, vol 60, p-1182–1188). In addition, these compounds exhibit a broad range of biological activities. (Kappe, C. O Tetrahedron, 1993, vol 49, p-6937–6963.) such as antiviral, antitumor, antibacterial and anti-inflammatory properties.
Dihydropyrimidinone compounds show a diverse range of biological activity. In recent years, however, interest in these compounds has increased rapidly, and the scope of the original cyclocondensation reaction has been widely extended by variation of all the compounds and conditions. The present popularity of these compounds is mainly due to their close structural relationship to the clinically important dihydropyrimidine calcium channel blockers of the nifedipine-type.
In 1893 Pietro Biginelli reported the first synthesis of 3,4-dihydropyrimidin-2(1H)-ones of compounds by a very simple one-pot condensation reaction of an aromatic aldehyde, urea and ethyl acetoacetate in ethanolic solution. Hence this type of compounds denoted as Biginelli compounds. However, the main draw back of Biginille reaction is unsatisfactory yields obtained in the case of substituted aromatic and aliphatic aldehydes (a. Wipf, P et al Tetrahedron Lett., 1995, vol 36, p-7819–7822; b. Folkers, K et al J. Am. Chem. Soc., vol 56, 1934, p-1180–1185). This has led to the disclosure of multi-step strategies (O Reilly, B. C et al Heterocycles 1987, vol 26, p-1185–1188.) that produce somewhat higher yields but lack the simplicity of the original Biginelli one-pot synthesis. At present several improved procedures have been reported such as Lewis Acids (a. ZrCl4: Reddy, Ch. V. et al Tetrahedron. Lett., 2002, vol 43, p-2657–2659; b. InBr3: Fu, N. Y. et al Tetrahedron 2002, vol 58, p-4801–4807; c. BiCl3: Rama Linga, K et al Synlett 2001, No. 6, p-863–865; d. LiClO4: Yadav. J. S et al Synthesis 2001, p-1341–1345; e. BF3-0Et2: Hu, E. H et al J. Org. Chem. 1998, vol 63, p-3454–3457), Triflates (a. La (OTf)3: Ma, Y et al J. Org. Chem., 2000, vol 65, p-3864–3868; b. Bi (OTf)3: Adapa, S. R et al Synlett 2002, p-67; c) Cu (OTf)2: Paraskar, A. S et al Tetrahedron Lett. 2003, vol 44, p-3305–3308.) and soluble polymer supported liquid phase synthesis (Xia, M et al Tetrahedron Lett. 2002, vol 43, p-7703–7705). However in spite of their potential utility, many of these methods involve expensive reagents, strongly acidic conditions, longer reaction times, and unsatisfactory yields. In recent years the development of more economical and environmental friendly conversion process is gaining interest in the chemical community.